Influence of Cytogenetic, Molecular Abnormalities and Other Risk Factors on the Outcomes of Children with Acute Myelogenous Leukemia Given An Unrelated Cord Blood Transplantation. A Survey on Behalf of Eurocord, ALWP and PDWP of EBMT
Notice bibliographique
Résumé
Abstract Abstract 834 Several cytogenetic and molecular abnormalities have a major prognostic implication in patients with AML treated with conventional chemotherapy. However, the impact of such aberrations on outcomes after unrelated cord blood transplantation (UCBT) is, currently, unknown. The purpose of this study was to analyze the outcomes and prognostic factors after UCBT for paediatric AML, with a special emphasis on cytogenetic and molecular abnormalities. We performed a retrospective multicentre study on 390 AML children, who received a single UCBT. Transplants were performed from 1994 through 2010 in EBMT centers. Median age was 6 years and median weight 22 Kg at time of transplant. At time of UCBT, 37% of patients were in CR1, 42% in CR2 and 21% in a more advanced disease status. In addition to hematological disease status classification, 253 children (65%) were stratified in unfavourable (35%), intermediate (22%) and favourable (8%) groups based on cytogenetic and molecular biology whenever possible. The majority of grafts were HLA 5/6 (44%) or 4/6 (37%) and 5% of patients received UCBT as a second transplant. Median infused total nucleated (TNC) and CD34+ cells were 4.95×107/kg and 1.9 ×105/kg of recipient body weight, respectively. The majority of patients (86%) received myeloablative conditioning regimen with TBI (26%) or busulphan (60%); ATG was used in 80% of cases. GvHD prophylaxis was included CSA+steroids in 70%, CsA+MMF in 17% and MTX+ others in 8% of patients. Median follow-up time was 24 months. The median time to achieve neutrophil and platelet recoveries was 24 and 42 days, respectively. Cumulative incidence (CI) of ANC recovery was 85%; in a multivariate model, it was favourably associated with a higher TNC dose (> median, HR: 1.40, p=.008) and transplantation in CR1 (HR: 1.39, p=.015). At day +100, CI of grade II–IV acute GvHD was 34% (11% grade III, 5% grade IV). At 2 years, CI of NRM (Non Relapse Mortality) was 24%. Multivariate analysis showed that TNC dose (>median, HR: 0.58, p=.024) and disease status at time of UCBT (CR1-2, HR: 0.55, p=.026) were associated with decreased NRM. There was a trend towards a decreased NRM in patients transplanted with a 6/6 or 5/6 HLA graft (p=.06). CI of relapse at 2 years was 17% for patients transplanted in CR1, 26% in CR2 and 44% in more advanced disease. Estimated 2 y-LFS was 63% in CR1, 43% in CR2 and 22% in more advanced disease patients. There was a trend towards a better LFS in patients receiving an UCBT with TNC >4.9 107/kg (>median, HR: 1.38, p=.05). The multivariate analysis identified favorable cytogenetic and molecular risk group (HR: 2.14, p=.03) and disease status at time of UCBT (advanced, HR: 0.44, p<.001) as factors independently associated with LFS. Forty nine children transplanted in CR1 with unfavourable disease had LFS of 70 ± 7%, not statistically different from the overall CR1 group. For those transplanted in CR2, 2y-LFS was 71 ± 9%, 33 ± 9% and 40 ± 7% in the favorable, intermediate and unfavorable subgroups, respectively. Multivariate analysis demonstrated the following significant prognostic factors: favorable cytogenetic and molecular risk group (HR: 3.74, p=.005) and previous CR1 duration longer than 7 months (first quartile, HR: 1.85, p=.03). These data demonstrate that UCBT is an attractive stem cell source for children with AML when no HLA-identical donor is available. The cell dose remains an important factor for engraftment and NRM. The results are particularly encouraging for the use UCBT in patients with unfavorable cytogenetic and molecular biology risk classification diseases in CR1. Disclosures: Mohty: Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».